Hernandez, Victor H. Gehrt, Anna Reuter, Kirsten Jing, Zhizi Jeschke, Marcus Schulz, Alejandro Mendoza Hoch, Gerhard Bartels, Matthias Vogt, Gerhard Garnham, Carolyn W. Yawo, Hiromu Fukazawa, Yugo Augustine, George J. Bamberg, Ernst Kuegler, Sebastian Salditt, Tim de Hoz, Livia Strenzke, Nicola Moser, Tobias 2024-01-20T10:04:38Z 2024-01-20T10:04:38Z 2022-01-10 2014-03 0021-9738 https://pubs.kist.re.kr/handle/201004/127023 Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. English AMER SOC CLINICAL INVESTIGATION INC RESTORES VISUAL RESPONSES MEDIATED GENE-TRANSFER INFERIOR COLLICULUS COCHLEAR IMPLANT ADENOASSOCIATED VIRUS SPEECH RECOGNITION TUNING CURVES HEARING CHANNELRHODOPSIN-2 NERVE Optogenetic stimulation of the auditory pathway Article 10.1172/JCI69050 1 JOURNAL OF CLINICAL INVESTIGATION, v.124, no.3, pp.1114 - 1129 JOURNAL OF CLINICAL INVESTIGATION 124 3 1114 1129 scie scopus 000332347700030 2-s2.0-84896786196 Medicine, Research & Experimental Research & Experimental Medicine Article RESTORES VISUAL RESPONSES MEDIATED GENE-TRANSFER INFERIOR COLLICULUS COCHLEAR IMPLANT ADENOASSOCIATED VIRUS SPEECH RECOGNITION TUNING CURVES HEARING CHANNELRHODOPSIN-2 NERVE